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Point mutation in the mouse glucocorticoid receptor preventing DNA binding impairs spatial memory.
M S Oitzl1, H M Reichardt, M Joëls
1Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, P.O. Box 9503, Leiden University Medical Center, 2300 RA Leiden, The Netherlands. m.oitzl@lacdr.leidenuniv.nl
Summary
Stress-induced activation of glucocorticoid receptors aids memory storage. DNA binding of the glucocorticoid receptor (GR) is crucial for this spatial memory enhancement, not protein interactions.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Endocrinology
Background:
- Glucocorticoid receptors (GR) mediate stress effects on memory.
- GR influence gene transcription via DNA binding and protein interactions.
- The specific GR mechanisms for memory facilitation remain unclear.
Purpose of the Study:
- To investigate the role of GR DNA binding versus protein interactions in spatial memory.
- To elucidate the molecular mechanisms of stress-induced memory enhancement.
Main Methods:
- Utilized male mutant mice (GR(dim/dim)) with impaired GR homodimerization and DNA binding.
- Assessed spatial memory using the water maze task.
- Measured locomotion, anxiety, and corticosterone levels.
- Administered exogenous corticosterone to adrenalectomized mice.
Main Results:
- Mutant mice exhibited impaired spatial memory compared to controls.
- Locomotion and anxiety levels were similar between genotypes.
- Mutant mice showed higher basal and stress-induced corticosterone levels.
- Exogenous corticosterone improved memory in controls but not mutants.
Conclusions:
- Task-related memory facilitation by corticosterone depends on GR DNA binding.
- GR protein-protein interactions are less critical for this memory effect.
- Disrupting GR DNA binding alone impairs spatial memory.